Canonical and non-canonical roles of oligodendrocyte precursor cells in mental disorders

Abstract

Psychiatric research has shifted from a neuroncentric view to understanding mental disorders as disturbances of heterogeneous brain networks. Oligodendrocyte precursor cells (OPCs)- actively involved in the modulation of neuronal functions - are altered in psychiatric patients, but the extent and related consequences are unclear. This review explores canonical and non-canonical OPC-related pathways in schizophrenia, bipolar disorder, post-traumatic stress disorder, and depression in humans, highlighting potential mechanisms shared across diagnostic entities.

Fig. 1. Search strategy.

Flow diagram of the searches of databases for the selection of the relevant research articles. The diagram reports the step-by-step screening of the relevant literature that was retrieved on PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://www.webofknowledge.com) with the reported search strings (see Supplementary Note 1). The diagram was adapted from the PRISMA guidelines for systematic review.

Fig. 2. Biometric analysis of the research articles published on the implication of OPCs in the onset of mental disorders.

A Representative confocal micrograph showing NG2-glia in the amygdala of an adult male C57Bl6/j mouse. Scale bar = 20 μm. B Graphical representation of the disease focus of the research articles included in this review (number of studies) plotted against the year of publication (SCZ = schizophrenia; MDD = major depressive disorder; BD = bipolar disorder; PTSD = post-traumatic stress disorder; Other = any mental disease other than SCZ, MDD, BD and PTSD). C Publication trend with respect to research articles investigating OPCs in psychiatry. Linear regression shows a mild but significant trend for an increase in the number of studies focusing on OPCs in mental illnesses related to the year of publication (R2 = 0.23, p = 0.02).

Fig. 3. Control search strategy.

Flow diagram of the searches of databases for the selection of the relevant research articles. The diagram reports the step-by-step screening of the relevant literature that was retrieved on PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://www.webofknowledge.com) with the reported control search strings (see Supplementary Note 2). The diagram was adapted from the PRISMA guidelines for systematic review.

Fig. 4. Graphical representation of the main findings in the oligodendrocyte lineage and mental illnesses.

The internal pie-chart shows the proportion and the number of studies that investigated the included mental diseases (SCZ = schizophrenia; MDD = major depressive disorder; BD = bipolar disorder; Other = PTSD + any mental disease other than SCZ, MDD, BD). Diseases are separated by colour and through thick black dashed lines. The outer pie-chart show the proportion of studies, within the specific pathology, that reported on either canonical/myelinogenic or non-canonical OPC functions. Canonical and non-canonical pathways are separated by colour and thin black dashed lines. This figure has been created with Biorender (https://www.biorender.com).